Mechanism of vascular smooth muscle contraction by sodium fluoride in the isolated aorta of rat and rabbit

A. S.O. Adeagbo, C. R. Triggle

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The purpose of this study was to determine the cellular basis for fluoride ion (F-)-induced contractions of isolated aortic rings from both the rat and the rabbit. The F- contractions were not affected by endothelial denudation but were enhanced in the presence of A+++ (0.1 or 1.0 mM) added to the bathing Krebs' solution. The contractile effect of F- also was not modified by bathing with Ca++-free + ethylene glycol bis(b-aminoethylether)-N,N-tetra-acetic acid Krebs' solution or nifedipine (10 μM), but was attenuated by inorganic (Cd++, Co++ and Ni++) Ca++ antagonists in normal and Ca++-free Krebs' media. Bis(o-aminophenoxy)-ethane-N-N-N'-N'-tetraacetic acid, ryanodine and intracellular Ca++ modulators, respectively, caused 36.1 ± 6.1%, 16.4 ± 6.8% and 52.3 ± 7.3% inhibition of the contractile response to F- in a Ca++-free media while causing near complete inhibition of norepinephrine-induced contractions. F- contractions were also inhibited by the calmodulin antagonists W-7 and calmidazolium (IC50 = 23.0 ± 7.0 and 45.0 ± 10.0 μM, respectively). On the other hand, the protein kinase C antagonists staurosporine and H-7 potently (IC50 = 0.016 ± 0.007 and 1.1 ± 0.5 μM, respectively) inhibited the fluoride-induced contractions. Aortic rings from the rabbit were similarly potently antagonized by the protein kinase C inhibitors, however, K+-induced contractions were also equally sensitive to these agents in both rat and rabbit tissues. The putative phospholipase C inhibitor neomycin was significantly less effective (IC50 = 13.0 ± 5.0, 0.44 ± 0.09 and 0.89 ± 0.40 mM) at inhibiting F- than norepinephrine and KCI contractile effects. F--induced contractions of aortic rings isolated from rats pretreated with pertussis toxin (50 μg/kg, i.v.) were not different from rings obtained from untreated rats. We conclude that the contraction elicited by F- most likely results from an alteration in the sensitivity of the contractile proteins to low or basal levels of Ca(i) possibly involving the activation of protein kinase C and/or the inhibition of phosphatase activity.

Original languageEnglish
Pages (from-to)66-73
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number1
Publication statusPublished - 1 Jan 1991

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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